Provided are methods and compositions for reducing the 
toxicity of certain hydrophobic therapeutic agents, especially 
polyene antibiotics, in particular, 
Amphotericin B (AmB), and therapeutics such as 
paclitaxel, 
tamoxifen, an acylated 
prodrug or an acylated cis-platin, by incorporating these agents within micelles comprising an amphiphilic block-forming 
copolymer. Where the 
polyene is 
amphotericin B, desirably the spacer is an 
alkyl molecule of aabout 2 to about 8 carbon atoms, desirably 6 carbon atoms, and the core is an N-
alkyl molecule of about 8 to about 28 carbon atoms, desirably 12 to 22 carbon atoms, advantageously, 12 to 18 carbon atoms, and as specifically embodied, 18 carbon atoms (
stearate moiety). For the formulation of a larger 
polyene, the spacer and core are proportionately larger than those for 
amphotericin B. As specifically exemplified herein, the 
polymer backbone is a PEO of about 270 units with about 10-30 core-forming PLAA subunits, and advantageously about 14-24. Desirably the 
stearate moiety has a substitution level on the 
copolymer from about 35 percent to about 70 percent.